The invention relates to a dual modality imaging apparatus, comprising a magnetic resonance imaging (=MRI) system and a fluorescence molecular tomography (=FMT) system, for investigating a sample located at a sample position,
wherein the MRI system comprises a magnet with a room temperature bore, with the sample position located within the bore,
and wherein the FMT system comprises means for directing a light beam towards the sample position, and a position-sensitive detector for collecting fluorescence light from the sample.
Such a device is known from Heng Xu et al., Applied Optics Vol. 44, No. 11 (2005), p. 2177-2188, see Ref. [12].
The combination of structural with functional and/or molecular imaging readouts enable proper allocation of functional or molecular information to tissue/organ structures and thereby the establishment (registration) of structure-function relationships. Clinically established examples are the combination of structural and functional Magnetic Resonance Imaging (MRI), where brain areas activated by a specific task are superimposed on high-resolution anatomical images, or the combination x-ray computer tomography (CT)/positron-emission tomography (PET) allowing locating areas of altered metabolic activity with regard to the overall anatomy. MRI/PET scanners are currently under evaluation both as clinical and preclinical imaging devices [1, 2].
The latter approaches using MRI as structural imaging method are attractive because i) MRI provides anatomical information of excellent soft-tissue contrast as its signal intensities are governed by several tissue-specific parameters, and ii) many MRI approaches yield functional/physiological information in addition. A limitation of PET as molecular imaging modality is the short half-life of positron emitting isotopes.
Small animal imaging fluorescence tomography has emerged as an alternative, in particular when using fluorophores absorbing and emitting in the far red or near-infrared range of the electromagnetic spectrum. Fluorescent markers are in general stable. Moreover, the fluorescent properties of a molecule depend on its environment, and therefore can be modulated through molecular interactions allowing the design of smart imaging probes that increase the sensitivity and selectivity of the imaging approach.
The inherent problem when using fluorescent imaging techniques in life animals is photon propagation in a highly scattering and absorbing medium such as tissue. Photons are transported as a diffusive wave rendering the extraction of geometrical information difficult. Yet, recent progress in modeling photon propagation in tissue allows for macroscopic imaging of whole animals (such as mice), the method being called fluorescence molecular tomography (FMT) [3].
Physical limitations of FMT with regard to spatial resolution and depth of light penetration into tissue due to absorption and scattering are compensated by the high sensitivity of the approach that might be used to derive specific information on molecular events which has been demonstrated in tumor models [4]. FMT can detect fluorophores at picomolar concentration and in contrast to PET allows multiplexing, i.e. the parallel detection of several fluorescent reporters with different emission wavelengths. Structural information can be used as a priori knowledge in image reconstruction improving the quality of diffuse optical tomography [5] and fluorescence molecular tomography [6]. Significant efforts are currently ongoing, combining FMT methods with x-ray CT as anatomical imaging modality [7].
In view of the strengths of the two modalities, combining MRI and FMT represents an attractive concept for small animal imaging. A recent publication by Niedre et al. [8] discusses recent developments in fluorescence-MR hybrid imaging, covering aspects of instrument design and development of dual-modality reporter probes. From the instrumentation point of view two strategies can be pursuit:
i) A fully integrated solution with the optical measurement taking place within the magnet. Both measurements are inherently co-registered and can be performed simultaneously under identical physiological conditions.
ii) The second approach uses an animal support compatible for both fluorescence and MR imaging [9]. In this case measurements are taken sequentially on dedicated systems. Assuming proper geometrical calibration of the two imaging modalities, image registration can be achieved by rigid body transformation.
Integrated fluorescence/MR imaging systems described to date use optical fibers that are brought into contact with the sample to guide light in and out of the magnet. They have been applied for diffuse optical spectroscopy measurements in subcutaneous tumors [10, 11]. A similar setup has been used by Heng et al. [12]: Their system for near-infrared tomography of rat brain uses a fiber bundle for light guiding in direct contact with the scalp.
Fiber based systems are inherently limited by a relative small number of source-detector pairs, preventing accurate spatial resolution as the maximum number of voxels that can be reconstructed is NS*ND, where NS and ND are the number of sources and detectors, respectively. In addition, the bulky fiber bundles have substantial space requirements, which may not be compatible with the small magnet bores commonly used in small animal MRI [13].
It is the object of the invention to provide a dual mode imaging apparatus which is simple in design and versatile in application, and in particular imposes less limitations on the maximum number of source/detector pairs during FMT imaging, thus allowing a better FMT image resolution.